This proposal focuses on the neuroanatomy and neurochemical control of offensive aggression. The first set of experiments will define the neural network(s), i.e., multiple populations of neurons throughout the central nervous system, that control offensive aggression. These studies will combine double and triple labeling of neurotransmitters and markers of cellular activity, together with retrograde and anterograde tracers. The neural network(s) controlling offensive aggression will be reconstructed using computer-assisted brain mapping. The functional significance of each component in the neural network will be determined by activating and blocking discrete populations of neurons. The second set of experiments will examine the interaction between vasopressin and serotonin in the control of offensive aggression. It is hypothesized that both neurotransmitter systems have reciprocal interactions that are critical for the modulation of offensive aggression - vasopressin facilitates fighting while serotonin diminishes fighting. These studies will combine site-specific microinjections of vasopressin and serotonin, immunoelectron microscopy to verify synaptic connections between vasopressin neurons and serotonin terminals, and labeling neurons that have both serotonin and vasopressin receptors. Violence in the United States is a national health problem. The studies outlined in this proposal should enhance our understanding of the neuroanatomy and neurochemical control of offensive aggression. There is evidence that the neural network controlling aggression is not static, but plastic; changes in environmental conditions continuously reshape pre- and postsynaptic elements to enhance and depress agonistic behavior. The predisposition toward aggressive and submissive behavior in certain environments may be mediated, in part, by alterations in the chemistry and synaptic connections between neurotransmitter systems. It is critical that we understand the environmental and biological conditions that influence agonistic behavior. Only then can we devise rational psychosocial and pharmacological therapies to help the victims of violent behavior and to understand better the neurobiology of individuals predisposed to violent behavior.